Obsessive Compulsive Treatment Efficacy Trial (OCTET) comparing the clinical and cost effectiveness of self-managed therapies: study protocol for a randomised controlled trial

Background: UK National Institute of Health and Clinical Excellence guidelines for obsessive compulsive disorder (OCD) specify recommendations for the treatment and management of OCD using a stepped care approach. Steps three to six of this model recommend treatment options for people with OCD that range from low-intensity guided self-help (GSH) to more intensive psychological and pharmacological interventions. Cognitive behavioural therapy (CBT), including exposure and response prevention, is the recommended psychological treatment. However, whilst there is some preliminary evidence that self-managed therapy packages for OCD can be effective, a more robust evidence base of their clinical and cost effectiveness and acceptability is required. Methods/Design: Our proposed study will test two different self-help treatments for OCD: 1) computerised CBT (cCBT) using OCFighter, an internet-delivered OCD treatment package; and 2) GSH using a book. Both treatments will be accompanied by email or telephone support from a mental health professional. We will evaluate the effectiveness, cost and patient and health professional acceptability of the treatments. Discussion: This study will provide more robust evidence of efficacy, cost effectiveness and acceptability of self-help treatments for OCD. If cCBT and/or GSH prove effective, it will provide additional, more accessible treatment options for people with OCD.

Improving mood with psychoanalytic and cognitive therapies (IMPACT): a pragmatic effectiveness superiority trial to investigate whether specialised psychological treatment reduces the risk for relapse in adolescents with moderate to severe unipolar depression: study protocol for a randomised controlled trial

Background Up to 70% of adolescents with moderate to severe unipolar major depression respond to psychological treatment plus Fluoxetine (20-50 mg) with symptom reduction and improved social function reported by 24 weeks after beginning treatment. Around 20% of non responders appear treatment resistant and 30% of responders relapse within 2 years. The specific efficacy of different psychological therapies and the moderators and mediators that influence risk for relapse are unclear. The cost-effectiveness and safety of psychological treatments remain poorly evaluated. Methods/Design Improving Mood with Psychoanalytic and Cognitive Therapies, the IMPACT Study, will determine whether Cognitive Behavioural Therapy or Short Term Psychoanalytic Therapy is superior in reducing relapse compared with Specialist Clinical Care. The study is a multicentre pragmatic effectiveness superiority randomised clinical trial: Cognitive Behavioural Therapy consists of 20 sessions over 30 weeks, Short Term Psychoanalytic Psychotherapy 30 sessions over 30 weeks and Specialist Clinical Care 12 sessions over 20 weeks. We will recruit 540 patients with 180 randomised to each arm. Patients will be reassessed at 6, 12, 36, 52 and 86 weeks. Methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, research assessors independent of treatment team and blind to randomization, analysis by intention to treat, data management using remote data entry, measures of quality assurance, advanced statistical analysis, manualised treatment protocols, checks of adherence and competence of therapists and assessment of cost-effectiveness. We will also determine whether time to recovery and/or relapse are moderated by variations in brain structure and function and selected genetic and hormone biomarkers taken at entry. Discussion The objective of this clinical trial is to determine whether there are specific effects of specialist psychotherapy that reduce relapse in unipolar major depression in adolescents and thereby costs of treatment to society. We also anticipate being able to utilise psychotherapy experience, neuroimaging, genetic and hormone measures to reveal what techniques and their protocols may work best for which patients.

An upgrade on the rabbit model of anthracycline-induced cardiomyopathy: shorter protocol, reduced mortality, and higher incidence of overt dilated cardiomyopathy

Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality.

Protocol for a feasibility study of a self help cognitive behavioural therapy resource for the reduction of dental anxiety in young people

Background Childhood dental anxiety is very common, with 10–20 % of children and young people reporting high levels of dental anxiety. It is distressing and has a negative impact on the quality of life of young people and their parents as well as being associated with poor oral health. Affected individuals may develop a lifelong reliance on general anaesthetic or sedation for necessary dental treatment thus requiring the support of specialist dental services. Children and young people with dental anxiety therefore require additional clinical time and can be costly to treat in the long term. The reduction of dental anxiety through the use of effective psychological techniques is, therefore, of high importance. However, there is a lack of high-quality research investigating the impact of cognitive behavioural therapy (CBT) approaches when applied to young people’s dental anxiety. Methods/design The first part of the study will develop a profile of dentally anxious young people using a prospective questionnaire sent to a consecutive sample of 100 young people referred to the Paediatric Dentistry Department, Charles Clifford Dental Hospital, in Sheffield. The second part will involve interviewing a purposive sample of 15–20 dental team members on their perceptions of a CBT self-help resource for dental anxiety, their opinions on whether they might use such a resource with patients, and their willingness to recruit participants to a future randomised controlled trial (RCT) to evaluate the resource. The third part of the study will investigate the most appropriate outcome measures to include in a trial, the acceptability of the resource, and retention and completion rates of treatment with a sample of 60 dentally anxious young people using the CBT resource. Discussion This study will provide information on the profile of dentally anxious young people who could potentially be helped by a guided self-help CBT resource. It will gain the perceptions of dental care team members of guided self-help CBT for dental anxiety in young people and their willingness to recruit participants to a trial. Acceptability of the resource to participants and retention and completion rates will also be investigated to inform a future RCT.

Protocol for ACCESS: a qualitative study exploring barriers and facilitators to accessing the emergency contraceptive pill from community pharmacies in Australia

Introduction The rate of unplanned pregnancy in Australia remains high, which has contributed to Australia having one of the highest abortion rates of developed countries with an estimated 1 in 5 women having an abortion. The emergency contraceptive pill (ECP) offers a safe way of preventing unintended pregnancy after unprotected sex has occurred. While the ECP has been available over-the-counter in Australian pharmacies for over a decade, its use has not significantly increased. This paper presents a protocol for a qualitative study that aims to identify the barriers and facilitators to accessing the ECP from community pharmacies in Australia. Methods and analysis Data will be collected through one-on-one interviews that are semistructured and in-depth. Partnerships have been established with 2 pharmacy groups and 2 women's health organisations to aid with the recruitment of women and pharmacists for data collection purposes. Interview questions explore domains from the Theoretical Domains Framework in order to assess the factors aiding and/or hindering access to ECP from community pharmacies. Data collected will be analysed using deductive content analysis. The expected benefits of this study are that it will help develop evidence-based workforce interventions to strengthen the capacity and performance of community pharmacists as key ECP providers. Ethics and dissemination The findings will be disseminated to the research team and study partners, who will brainstorm ideas for interventions that would address barriers and facilitators to access identified from the interviews. Dissemination will also occur through presentations and peer-reviewed publications and the study participants will receive an executive summary of the findings. The study has been evaluated and approved by the Monash Human Research Ethics Committee.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Cross layer based protocols for energy aware and critical data delivery related applications using wireless sensor networks

Wireless Sensor Networks (WSNs) have been an exciting topic in recent years. The services offered by a WSN can be classified into three major categories: monitoring, alerting, and information on demand. WSNs have been used for a variety of applications related to the environment (agriculture, water and forest fire detection), the military, buildings, health (elderly people and home monitoring), disaster relief, and area or industrial monitoring. In most WSNs tasks like processing the sensed data, making decisions and generating emergency messages are carried out by a remote server, hence the need for efficient means of transferring data across the network. Because of the range of applications and types of WSN there is a need for different kinds of MAC and routing protocols in order to guarantee delivery of data from the source nodes to the server (or sink). In order to minimize energy consumption and increase performance in areas such as reliability of data delivery, extensive research has been conducted and documented in the literature on designing energy efficient protocols for each individual layer. The most common way to conserve energy in WSNs involves using the MAC layer to put the transceiver and the processor of the sensor node into a low power, sleep state when they are not being used. Hence the energy wasted due to collisions, overhearing and idle listening is reduced. As a result of this strategy for saving energy, the routing protocols need new solutions that take into account the sleep state of some nodes, and which also enable the lifetime of the entire network to be increased by distributing energy usage between nodes over time. This could mean that a combined MAC and routing protocol could significantly improve WSNs because the interaction between the MAC and network layers lets nodes be active at the same time in order to deal with data transmission. In the research presented in this thesis, a cross-layer protocol based on MAC and routing protocols was designed in order to improve the capability of WSNs for a range of different applications. Simulation results, based on a range of realistic scenarios, show that these new protocols improve WSNs by reducing their energy consumption as well as enabling them to support mobile nodes, where necessary. A number of conference and journal papers have been published to disseminate these results for a range of applications.